The development and application of new molecularly based therapies is of utmost important. The key to the development of such rational therapeutic approaches lies in the identification of suitable molecular markers. Though it has been long established that tumor progression is angiogenesis dependent, fundamental questions remain regarding the characteristic differences between normal and tumor endothelial cells. Thus, novel markers, which can distinguish between normal and tumor vascular endothelium, are needed. Importantly, these markers might provide potential therapeutic targets for anti-vascular therapy. Magic roundabout (MRB) is a roundabout receptor family member with endothelial cell restricted expression. Our preliminary data shows that the MRB is highly expressed in tumor endothelium and is markedly diminished or absent in normal endothelium. Therefore in specific aim 1, we propose to take advantage of MRB's tumor endothelial restricted expression to test the hypothesis that MRB expression can be used for in vivo molecular imaging of tumor endothelium. It is expected that investing our resources in developing MRB as a tumor vascular imaging target might provide a tool to monitor the efficacy of various antiangiogenic/ vascular therapies. In specific aim 2, we propose to isolate other tumor endothelium markers (TEMs) candidates from primary renal cell cancer (RCC) and assess their expression at sites of RCC metastasis. It is hoped that some of these TEMs may serve as anti-angiogenic targets for RCC metastasis therapy.